Effect of macrophage migration inhibitory factor on inflammatory cytokines and fibrogenic gene expression in human RPE cells

Qin,Dong; Jiang,Yanrong; Jin,Xuemin

doi:10.3892/mmr.2019.10277

Effect of macrophage migration inhibitory factor on inflammatory cytokines and fibrogenic gene expression in human RPE cells

Authors:
- Dong Qin
- Yanrong Jiang
- Xuemin Jin
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Affiliations: Henan Eye Institute, Henan Provincial Eye Hospital, People's Hospital of Henan Province, Zhengzhou, Henan 450003, P.R. China, Department of Ophthalmology, People's Hospital of Peking University, Beijing 100044, P.R. China
Published online on: May 22, 2019 https://doi.org/10.3892/mmr.2019.10277
Pages: 830-836

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Abstract

Proliferative vitreoretinopathy (PVR) is a vision‑threatening disease. It is also a common complication resulting from surgery to correct rhegmatogenous retinal detachment. Proliferation and migration of retinal pigment epithelial (RPE) cells and the secretion of extracellular matrix molecules play an important role in the formation of the preretinal membrane in PVR patients. Furthermore, upregulated expression of inflammatory cytokines within the vitreous or subretinal fluid of patients experiencing vitreoretinal disorders may aggravate the inflammatory response and be involved in the development of PVR. PVR is triggered by many inflammatory cytokines and growth factors. Macrophage migration inhibitory factor (MIF), an inflammatory cytokine, is upregulated in the vitreous in PVR patients. However, there is little known concerning the connection between MIF and the expression of inflammatory cytokines, interleukin‑6 (IL‑6) and monocyte chemotactic‑1 (MCP‑1), and the fibrogenic gene, collagen I, in human RPE cells. Cell proliferation, migration, and expression of IL‑6, MCP‑1 and collagen I were assessed using an MTT assay, a Transwell assay, real‑time PCR analysis and ELISA kits. Western‑blot analysis was used to detect phosphorylation of p38 mitogen activated protein kinase (MAPK) and extracellular signal‑regulated kinase (ERK) signaling pathways. The data revealed that MIF promoted the proliferation, migration and expression of IL‑6, MCP‑1 and collagen I, and phosphorylation of p38 and ERK signaling pathways in RPE cells in vitro. These findings suggest that MIF plays a proinflammatory and profibrotic role in the development of PVR.

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1	Ishikawa K, He S, Terasaki H, Nazari H, Zhang H, Spee C, Kannan R and Hinton DR: Resveratrol inhibits epithelial mesenchymal transition of retinal pigment epithelium and development of proliferative vitreoretinopathy. Sci Rep. 5:163862015. View Article : Google Scholar : PubMed/NCBI
2	Ryan SJ: The pathophysiology of proliferative vitreoretinopathy in its management. Am J Ophthalmol. 100:188–193. 1985. View Article : Google Scholar : PubMed/NCBI
3	Newsome DA, Rodrigues MM and Machemer R: Human massive periretinal proliferation. In vitro characteristics of cellular components. Arch Ophthalmol. 99:873–880. 1981. View Article : Google Scholar : PubMed/NCBI
4	Ricker LJ, Kessels AG, de Jager W, Hendrikse F, Kijlstra A and La Heij EC: Prediction of proliferative vitreoretinopathy after retinal detachment surgery: Potential of biomarker profiling. Am J Ophthalmol. 154:347–354.e2. 2012. View Article : Google Scholar : PubMed/NCBI
5	Ricker LJ, Altara R, Goezinne F, Hendrikse F, Kijlstra A and La Heij EC: Soluble apoptotic factors and adhesion molecules in rhegmatogenous retinal detachment. Invest Ophthalmol Vis Sci. 52:4256–4262. 2011. View Article : Google Scholar : PubMed/NCBI
6	Ricker LJ, Kijlstra A, de Jager W, Liem AT, Hendrikse F and La Heij EC: Chemokine levels in subretinal fluid obtained during scleral buckling surgery after rhegmatogenous retinal detachment. Invest Ophthalmol Vis Sci. 51:4143–4150. 2010. View Article : Google Scholar : PubMed/NCBI
7	Bromberg-White JL, Glazer L, Downer R, Furge K, Boguslawski E and Duesbery NS: Identification of VEGF-independent cytokines in proliferative diabetic retinopathy vitreous. Invest Ophthalmol Vis Sci. 54:6472–6480. 2013. View Article : Google Scholar : PubMed/NCBI
8	Hoerster R, Hermann MM, Rosentreter A, Muether PS, Kirchhof B and Fauser S: Profibrotic cytokines in aqueous humour correlate with aqueous flare in patients with rhegmatogenous retinal detachment. Br J Ophthalmol. 97:450–453. 2013. View Article : Google Scholar : PubMed/NCBI
9	Ricker LJ, Kijlstra A, Kessels AG, de Jager W, Liem AT, Hendrikse F and La Heij EC: Interleukin and growth factor levels in subretinal fluid in rhegmatogenous retinal detachment: A case-control study. PLoS One. 6:e191412011. View Article : Google Scholar : PubMed/NCBI
10	Symeonidis C, Papakonstantinou E, Androudi S, Georgalas I, Rotsos T, Karakiulakis G, Diza E and Dimitrakos SA: Comparison of interleukin-6 and matrix metalloproteinase expression in the subretinal fluid and the vitreous during proliferative vitreoretinopathy: Correlations with extent, duration of RRD and PVR grade. Cytokine. 67:71–76. 2014. View Article : Google Scholar : PubMed/NCBI
11	David J: Delayed hypersensitivity in vitro: Its mediation by cell-free substances formed by lymphoid cell-antigen interaction. Proc Natl Acad Sci USA. 56:72–77. 1966. View Article : Google Scholar : PubMed/NCBI
12	Bloom B and Bennet B: Mechanism of a reaction in vitro associated with delayed-type hypersensitivity. Science. 153:80–82. 1966. View Article : Google Scholar : PubMed/NCBI
13	Nishihira J, Koyama Y and Mizue Y: Identification of macrophage migration inhibitory factor (MIF) in human vascular endothelial cells and its induction by lipopolysaccharide. Cytokine. 10:199–205. 1998. View Article : Google Scholar : PubMed/NCBI
14	Abe R, Shimizu T, Ohkawara A and Nishihira J: Enhancement of macrophage migration inhibitory factor (MIF) expression in injured epidermis and cultured fibroblasts. Biochimica Biophysica Acta. 1500:1–9. 2000. View Article : Google Scholar
15	Onodera S, Suzuki K, Matsuno T, Kaneda K, Kuriyama T and Nishihira J: Identification of macrophage migration inhibitory factor in murine neonatal calvariae and osteoblasts. Immunology. 89:430–435. 1996. View Article : Google Scholar : PubMed/NCBI
16	Bernhagen J, Calandra T, Mitchell RA, Martin SB, Voelter W, Manogue KR, Cerami A and Bucala R: MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature. 365:756–759. 1993. View Article : Google Scholar : PubMed/NCBI
17	Barnes MA, McMullen MR, Roychowdhury S, Madhun NZ, Niese K, Olman MA, Stavitsky AB, Bucala R and Nagy LE: Macrophage migration inhibitory factor is required for recruitment of scar-associated macrophages during liver fibrosis. J Leukoc Biol. 97:161–169. 2015. View Article : Google Scholar : PubMed/NCBI
18	Olivieri C, Bargagli E, Inghilleri S, Campo I, Cintorino M and Rottoli P: Macrophage migration inhibitory factor in lung tissue of idiopathic pulmonary fibrosis patients. Exp Lung Res. 42:263–266. 2016. View Article : Google Scholar : PubMed/NCBI
19	Shimizu T, Nishihira J, Watanabe H, Abe R, Honda A, Ishibashi T and Shimizu H: Macrophage migration inhibitory factor is induced by thrombin and factor Xa in endothelial cells. J Biol Chem. 279:13729–12737. 2004. View Article : Google Scholar : PubMed/NCBI
20	Matsuda A, Tagawa Y, Matsuda H and Nishihira J: Identification and immunohistochemical localization of macrophage migration inhibitory factor in human cornea. FEBS Lett. 385:225–228. 1996. View Article : Google Scholar : PubMed/NCBI
21	Matsuda A, Tagawa Y, Yoshida K, Matsuda H and Nishihira J: Expression of macrophage migration inhibitory factor in rat retina and its immunohistochemical localization. J Neuroimmunol. 77:85–90. 1997. View Article : Google Scholar : PubMed/NCBI
22	Mitamura Y, Takeuchi S, Matsuda A, Tagawa Y, Mizue Y and Nishihira J: Macrophage migration inhibitory factor levels in the vitreous of patients with proliferative vitreoretinopathy. Am J Ophthalmol. 128:763–765. 1999. View Article : Google Scholar : PubMed/NCBI
23	Veillat V, Carli C, Metz CN, Al-Abed Y, Naccache PH and Akoum A: Macrophage migration inhibitory factor elicits an angiogenic phenotype in human ectopic endometrial cells and triggers the production of major angiogenic factors via CD44, CD74, and MAPK signaling pathways. J Clin Endocrinol Metab. 95:E403–E412. 2010. View Article : Google Scholar : PubMed/NCBI
24	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
25	Chung BH, Kim JD, Kim CK, Kim JH, Won MH, Lee HS, Dong MS, Ha KS, Kwon YG and Kim YM: Icariin stimulates angiogenesis by activating the MEK/ERK-and PI3K/Akt/eNOS-dependent signal pathways in human endothelial cells. Biochem Biophys Res Commun. 376:404–408. 2008. View Article : Google Scholar : PubMed/NCBI
26	Fekrat S, de Juan E Jr and Campochiaro PA: The effect of oral 13-cis-retinoic acid on retinal redetachment after surgical repair in eyes with proliferative vitreoretinopathy. Ophthalmology. 102:412–418. 1995. View Article : Google Scholar : PubMed/NCBI
27	Wiedemann P, Hilgers RD, Bauer P and Heimann K: Adjunctive daunorubicin in the treatment of proliferative vitreoretinopathy: Results of a multicenter clinical trial. Daunomycin Study Group. Am J Ophthalmol. 126:550–559. 1998. View Article : Google Scholar : PubMed/NCBI
28	Asaria RH, Kon CH, Bunce C, Charteris DG, Wong D, Khaw PT and Aylward GW: Adjuvant 5-fluorouracil and heparin prevents proliferative vitreoretinopathy: Results from a randomized, double-blind, controlled clinical trial. Ophthalmol. 108:1179–1183. 2001. View Article : Google Scholar
29	Chang YC, Kao YH, Hu DN, Tsai LY and Wu WC: All-trans retinoic acid remodels extracellular matrix and suppresses laminin-enhanced contractility of cultured human retinal pigment epithelial cells. Exp Eye Res. 8:900–909. 2009. View Article : Google Scholar
30	Sadaka A and Giuliari GP: Proliferative vitreoretinopathy: Current and emerging treatments. Clin Ophthalmol. 6:1325–1333. 2012.PubMed/NCBI
31	Chang YC, Hu DN and Wu WC: Effect of oral 13-cis-retinoic acid treatment on postoperative clinical outcome of eyes with proliferative vitreoretinopathy. Am J Ophthalmol. 146:440–446. 2008. View Article : Google Scholar : PubMed/NCBI
32	Kishimoto T: Interleukin-6: Discovery of a pleiotropic cytokine. Arthritis Res Ther. 8 (Suppl 2):S22006. View Article : Google Scholar : PubMed/NCBI
33	Kuppner MC, McKillop-Smith S and Forrester JV: TGF-beta and IL-1 beta act in synergy to enhance IL-6 and IL-8 mRNA levels and IL-6 production by human retinal pigment epithelial cells. Immunology. 84:265–271. 1995.PubMed/NCBI
34	Holtkamp GM, Van Rossem M, de Vos AF, Willekens B, Peek R and Kijlstra A: Polarized secretion of IL-6 and IL-8 by human retinal pigment epithelial cells. Clin Exp Immunol. 112:34–43. 1998. View Article : Google Scholar : PubMed/NCBI
35	Romano M, Sironi M, Toniatti C, Polentarutti N, Fruscella P, Faggioni R, Luini W, van Hinsbergh V, Sozzani S, Bussolino F, et al: Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity. 6:315–325. 1997. View Article : Google Scholar : PubMed/NCBI
36	Deshmane SL, Kremlev S, Amini S and Sawaya BE: Monocyte chemoattractant protein-1 (MCP-1): An overview. J Interferon Cytokine Res. 29:313–326. 2009. View Article : Google Scholar : PubMed/NCBI
37	Han QH, Hui YN, Du HJ, Zhang WJ, Ma JX and Wang SY: Migration of retinal pigment epithelial cells in vitro modulated by monocyte chemotactic protein-1: Enhancement and inhibition. Graefes Arch Clin Exp Ophthalmol. 239:531–538. 2001. View Article : Google Scholar : PubMed/NCBI
38	Mitamura Y, Takeuchi S, Yamamoto S, Yamamoto T, Tsukahara I, Matsuda A, Tagawa Y, Mizue Y and Nishihira J: Monocyte chemotactic protein-1 levels in the vitreous of patients with proliferative vitreoretinopathy. Jpn J Ophthalmol. 46:218–221. 2002. View Article : Google Scholar : PubMed/NCBI
39	Xie J, Yang L, Tian L, Li W, Yang L and Li L: Macrophage migration inhibitor factor upregulates MCP-1 expression in an autocrine manner in hepatocytes during acute mouse liver injury. Sci Rep. 6:276652016. View Article : Google Scholar : PubMed/NCBI
40	Zhang Y, Gu R, Jia J, Hou T, Zheng LT and Zhen X: Inhibition of macrophage migration inhibitory factor (MIF) tautomerase activity suppresses microglia-mediated inflammatory responses. Clin Exp Pharmacol Physiol. 43:1134–1144. 2016. View Article : Google Scholar : PubMed/NCBI
41	Ko JA, Sotani Y, Ibrahim DG and Kiuchi Y: Role of macrophage migration inhibitory factor (MIF) in the effects of oxidative stress on human retinal pigment epithelial cells. Cell Biochem Funct. 35:426–432. 2017. View Article : Google Scholar : PubMed/NCBI